Mesoderm and EndodermOrganogenesisGonadal tissue (genital ridge)derives from intermediate mesodermFormationof the chickheart fromsplanchniclateral platemesodermCardiogenicmesoderm isinduced byBMP and FGFsignals fromadjacentanteriorendodermFusion of theendocardialprimordiacreates theinner lining ofthe heart(endocardium)Fusion of themesocardiumforms acontinuousmyocardiumthat will giverise to heartmuscleNkx2-5 crucial for heart developmentLeft-right assymetry of the heartNodal mRNA Pitx2 mRNAL RLRThe right to left flow in the mouse nodecarries little “parcels” loaded with Shh andRetinoic acid (Gilbert pp. 347-347, 364-366)Origin and migration of thehematopoietic stem cells (HSC)Aorta-gonad-mesonephrosFunctions of the endoderm• Participates in the formation of mesodermalorgans (notochord, heart)• Constructs the linings of the digestive andrespiratory tubesMajor derivatives ofthe endoderm• Digestive tube: esophagus, stomach, smallintestine, colon; tonsils, thyroid, thymus,parathyroid glands (pharynx); liver, pancreas,gallbladder• Respiratory tube: trachea, bronchi, alveoli oflungsPharynx derivatives• Middle ear cavity• Tonsils• Thyroid• Thymus• Respiratory tractPartitioning of the foregut intoesophagus and respiratory tract (week3-4 of human gestation)Techniques• Whole mount in situ hybridization• RNA interferenceCAPE evaluations• Please answer the following questions:Which of the following factors candirect the female sex determination?• A. Presence of two identical sexchromosomes (XX)• B. Presence of two unmatched sexchromosomes (ZW)• C. Temperature at which the embryodevelops• D. Single or double set of chromosomes• All of the aboveTemperature dependent sexdeterminationSexual Differentiation in Mammals• Primary sex determination: Specification ofthe gonads; whether they differentiate asovaries or testes• Secondary sex determination: Specificationof body phenotype for sexually dimorphicstructures outside the gonadsGonadal tissue (genital ridge)derives from intermediate mesodermhttp://www.med.unc.edu/embryo_images/unit-genital/genital_htms/genital008a.htmThe indifferentstage of humangonadaldevelopmentCord cells become granulosacellsmesenchymal cells becomethecal cells - estrogen producingcellstogether, these form the ovarianfolliclesGonadaldevelopment inXX individualGonadaldevelopment inXY individualCord cells become Sertoli cells -develop into testes cords, wheregerm cells differentiate intosperm, secrete AMH Mesenchymal cells becomeLeydig cells - secretetestosteroneSRY: Sex determining Region on the YchromosomeSome of the evidence that SRY is the testis-determining factor:• Present in males, absent in females• Loss of function: human XY females havemutations in SRY protein• Gain of function: XX mouse transgenic for Sryare malesSry is only part of the storySox9 is a transcriptional factor related to SryInitially expressed in indifferent gonads, maintained onlyin testesEvolutionary conservedProbably activated by SryLoss results in sex reversalsDAX1 is a potentialtestis-suppressing geneDAX1 is atranscritpionalfactor. Initiallyexpressed in bothsexes, maintainedonly in ovary.Was foundbecause itsduplications lead tofemale phenotypein XY individualsMammalian genital ducts atthe sexually indifferent stageGenital duct development inXY and XX individualsll llIn males, testosterone inhibits Wolffian duct!s degeneration, AMH induces Mullerianduct to regress.In females, estrogen induces differentiation of Mullerian duct. Wolffian